Increased Lipid Peroxidation in Patients with Pulmonary Hypertension

Abstract

Isoprostanes are chemically stable lipid peroxidation products of arachidonic acid, the quantification of which provides a novel approach to the assessment of oxidative stress in vivo. The main objective of this study was to quantify the urinary levels of isoprostaglandin F(2alpha) type III (iPF(2alpha)-III), an F(2)-isoprostane, in patients with pulmonary hypertension (PHT) in comparison with healthy controls. The secondary objective was to test whether baseline iPF(2alpha)-III levels correlate to the reversibility of pulmonary hypertension in response to inhaled NO challenge. Urinary iPF(2alpha)-III levels were measured by gas chromatography-mass spectrometry in 25 patients with PHT, 14 of whom were investigated for response to inhaled NO challenge. Urinary iPF(2alpha)-III levels in PHT patients (225 +/- 27 pmol/mmol creatinine) were 2.3 times as high as in controls (97 +/- 7 pmol/mmol creatinine, p < 0.001). The mean pulmonary arterial pressure variation and the pulmonary vascular resistance variation in response to inhaled NO were correlated to basal iPF(2alpha)-III levels. This study shows that oxidative stress is increased in patients with pulmonary hypertension. Furthermore, iPF(2alpha)-III levels inversely correlate to pulmonary vasoreactivity. These observations are consistent with the hypothesis that free radical generation is involved in PHT pathogenesis.

Increased isoprostane levels in oleic acid-induced lung injury

“…It has been reported that isoprostane is a modest pulmonary vasoconstrictor [10][11][12] and the levels in urine were increased in patients with pulmonary hypertension [9]. In the present study, mild pulmonary hypertension persisted after oleic acid administration [14].…”

“…A number of studies have shown these compounds to be extremely accurate markers of lipid peroxidation in animal models of acute lung injury (ALI) [4,5] and have revealed the role of oxidant injury in pulmonary diseases [6][7][8][9], including pulmonary vascular diseases such as ALI and/or adult respiratory distress syndrome (ARDS) and pulmonary hypertension. The levels of breath condensate or lung fluid isoprostanes are significantly elevated in patients with ALI/ARDS [6][7][8].…”

“…The levels of breath condensate or lung fluid isoprostanes are significantly elevated in patients with ALI/ARDS [6][7][8]. Isoprostane levels in urine are increased in patients with pulmonary hypertension [9]. In addition, the increases are inversely correlated with pulmonary vasoreactivity as measured by decreased pulmonary vascular resistance in response to inhaled nitric oxide.…”

Contribution of xanthine oxidase-derived superoxide to chronic hypoxic pulmonary hypertension in neonatal rats

“…A putative role for oxidative stress is also supported by observational studies in adult humans with idiopathic PHT (7,10). The injured pulmonary vasculature is known to be a major source of ROS, particularly superoxide anion (O 2 •Ϫ ).…”

Urinary F2-isoprostanes are poor prognostic indicators for the development of bronchopulmonary dysplasia

“…Although F 2 -IsoP and 8-iso-PGF 2a have been identified as an index of lipid peroxidation in numerous adult pulmonary diseases, [7][8][9][10] limited data are available on the role of F 2 -IsoP as a marker of BPD in premature infants. We hypothesized that premature infants <30-weeks gestation that later develop BPD would have elevated levels of urinary 8-iso-PGF 2a early in life, when compared to those infants who do not develop BPD.…”